Inositol-phosphoglycan (IPG) is a putative mediator of insulin action that has been shown to affect numerous biochemical processes. IPG, prepared from liver membranes, promptly inhibited phenylephrine- or vasopressin-induced [Ca2+](i) oscillations when perfused over Fura-2-dextran injected rat hepatocytes. An antibody to IPG suppressed the inhibitory effect of insulin on the [Ca2+](i) oscillations. Measurement of the rate of quench of cytoplasmic Fura-2 by extracellular Mn2+ showed that Ca2+ entry occurred continuously in the unstimulated cell and was not affected by phenylephrine or vasopressin. IPG, specifically, almost completely abolished the Mn2+ quench rate. Elevated extracellular [Ca2+] reversed the inhibitory effect of IPG on [Ca2+](i) oscillations. We conclude that IPG inhibits the hepatocyte Ca2+ oscillator by reducing the continuous Ca2+ influx that is required to sustain oscillations in [Ca2+].

This work was supported, in part, by grants from DGICYT, Europharma, Comunidades Autónomas de Madrid y Canarias (IM), Acción Integrada Hispano-Británica, the British Council, and The Wellcome Trust.

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